Colorectal cancer is a major health problem with over 1.2 million new cases and 608,700 deaths estimated every year in the world. Despite the surgical resection of the primary tumour, around 50% of patients die within five years of diagnosis as a result of local tumour recurrences or distant metastasis. This high mortality is mainly due to a lack of efficient test allowing the detection of patients at an early stage of the disease. Thus, there is an urgent need for new early markers that will help to identify patients with high risk for developing colorectal cancer.
In the general population the most frequently occurring lesion in the colon is the hyperplastic polyp (HP), with prevalence in western populations of 10% to 35%. Hyperplastic polyps (including globlet cell-rich HP, microvesicular HP and mucin poor HP) have long been considered as innocuous lesions with no malignant potential, whereas adenomatous polyps (including tubular, villous, tubulovillous and serrated adenomas) were recognized as neoplastic precursor lesions for colorectal adenocarcinomas.
However, large HP (size>1 cm) and the presence of multiple HP (number>5) in hyperplastic polyposis syndrome have been clearly associated with colorectal adenomas or adenocarcinoma [Renaut A J et al., 2002]. Based on these considerations, in France, clinical practice guidelines from the French National Agency for Accreditation and Evaluation in Healthcare do not recommend colonoscopy for patients with HP, except after resection of one large hyperplastic polyp (≧1 cm) and/or multiple polyps (n≧5) or if there is a family history of hyperplastic polyps. Neither does the American College of gastroenterology [Bond J H 2000 and Rex D K, et al., 2009].
In addition to the cases of large HP and hyperplastic polyposis, more recent studies have suggested a link between HP and sporadic colorectal cancer. Huang, et al. also found that patients with HP on initial colonoscopic examination have an increased incidence of colorectal adenomas on follow-up colonoscopy. However Huang, et al study does not allow to determine which HP is at high risk and do not identify the patients with HP that will develop colonic neoplasia (adenomas/carcinomas) after resection of these initial polyps. Until now, there is no biomarker to predict which HP may have a malignant potential and to identify the subset of patients with HP that will develop colonic neoplasia after resection of these initial polyps and for which a more suitable follow up strategy could be considered (about 40% of the patients according to our study and Huang study). It is also important to identify the 60% of patients with HP that will not develop adenomas or carcinomas after resection of these initial HP because there is no need for these patients to propose a colonoscopy follow up. The current invention identifies and validates such a biomarker.
The hormone precursor progastrin (PG) is recognized as a growth factor which plays an important promoting role in colon carcinogenesis. This hormone precursor is overexpressed in colorectal adenomatous polyps (neoplastic polyps) and carcinomas [Nemeth J. et al., 1993; Siddheshwar R K et al., 2001 and Van Solinge W W et al. 1993. In contrast this prohormone is absent from the healthy colonic tissues. The expression or overexpression of progastrin has never been reported in non neoplastic lesions and in particular in HP neither in human samples nor in animal models. US Patent No US2010/0291193 discloses the presence of negligible to moderate levels of gastrin mRNA in normal colonic mucosa not significantly different from the mRNA levels observed in a sample of 10 HP. Moreover, no progastrin immunostaining is shown in HP.